News and Events BMDCR
Huggins Lecture Series
Saturdays, January 17 through March 13, 2004
|
 |
Easy bruising, abnormal scarring, loose joints and brittle bones are the major clinical findings in patients suffering from a subset of Ehlers-Danlos syndrome (EDS) and osteogenesis imperfecta (OI). These heritable disorders of connective tissue are caused by a mutation in the gene(s) coding for type I collagen, the most abundant protein in the human body. There are currently no effective treatments for these diseases. In order to identify possible therapeutic approaches for these debilitating conditions, we developed an in vitro model, which mimics the collagen-deficient environment present in EDS and OI. Through the analysis of cellular DNA, we found 5 genes that correlate with increased tissue formation, a desired therapeutic effect in EDS and OI.
Identification of the effect of proteins encoded by these genes in our in vitro model could represent a major step in the development of new strategies for EDS/OI. An understanding of the tissue stimulating properties of collagen-synthesis stimulating proteins in EDS and OI, and the precise mechanisms by which they affects disease, may give us important information about normal collagen metabolism in tissues. These processes are also of critical importance during human development, wound healing, and aging.
Melanoma is the most common cause of death from cutaneous malignancy, and is the cancer that is most rapidly rising in incidence, a trend likely to continue over subsequent years. Melanoma accounts for roughly 5% of all skin cancers and 1% of all malignant tumors. The most important nature of melanoma is its extremely high potential to develop metastasis, which is associated with a poor prognosis. Thus, pharmaceutical intervention of mechanisms involved in melanoma progression would represent an important contribution to established public health programs effective in prevention and early detection.
Recent reports have demonstrated the presence of activating mutations in t genes encoding for kinases in 60-70% of human melanomas. These genes encode for proteins member of pathways such as the Ras-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway family of serine/threonine kinases, which have been implicated in the control of cell proliferation, differentiation and survival. The importance of physiologic kinase-mediated signaling is underscored in knockout mice studies, in which BRAF gene disruption resulted in death in utero due to vascular deficiencies. Using RNA interference methods, Hingorani et al. were able to abrogate the malignant phenotype in the BRAF mutation-harboring WM793 melanoma cell line. The in vitro and in vivo data strongly support the concept of targeted inhibition of kinases in melanoma, as efficacy would be obtained with minimal toxicity.
Untangling the Roots of Cancer |
January 17, 2004 |
View Adobe PDF
View Flash Paper
| Carcinogenesis | January 24, 2004 |
| Skin Cancer | January 31, 2004 |
| Research and Diagnostic Tools | February 14, 2004 |
| Life and Death in Cancer Cells | February 21, 2004 |
| Blood Vessel Formation and Metastasis | February 28, 2004 |
| The Immune System and Cancer | March 6, 2004 |
| Armamentarium Against Cancer | March 13, 2004 |